Evolution of the immunoglobulin kappa light chain locus in the rabbit: evidence for differential gene conversion events.

Abstract

The rabbit kappa light chain gene family is characterized by the presence of two constant region (C kappa) genes; the C kappa 1 gene encodes the constant region of the principal rabbit immunoglobulin light chain, the C kappa 2 gene being not or very poorly expressed in domestic rabbits. There exist four major K1 alleles (b4, b5, b6, and b9), which are unequally expressed in heterozygous rabbits at the K1 locus. Here, we compare the nucleotide sequences of the joining (J) clusters of the kappa light chain gene (J kappa) linked to the b4K2 locus and to the b4 and b9 alleles at the K1 locus. As for C kappa genes, there is evidence for intergenic conversion between the J kappa 1 and J kappa 2 clusters as well as maximum divergence in the expressed J segments. The b9 J kappa 1 cluster differs from its b4 counterpart in that two out of the five J kappa segments (J1 and J2) are expressed instead of only one. This implies that preferential expression of the b4 allele as compared to the b9 allele is not only correlated to the number of available J kappa pieces. The b9 J2 segment is functional in spite of the presence of a termination codon immediately upstream of its coding region. Two major structural differences were observed between the J-C intron sequences of the b9 and b4 alleles; namely a 160-base-pair deletion of an A + T-rich sequence in b9 (which also occurs in the K2 locus) and a 10-base-pair deletion plus some substitutions in the region corresponding to the mouse kappa intron activating element. These differences could underlie the lower transcriptional rate of the b9 allele.